B the intracellular osmotic pressure and thereby restoring cell volume to normal. Conversely with cell shrinking a regulatory volume increase response transports osmolytes into the cell, raising the intracellular osmotic pressure and thereby restoring cell volume to normal. These osmolytes include ions and organic molecules such as polyols (sorbitol and myo-inositol), methylamines (glycerophosphorylcholine and betaine), and some amino acids (taurine, glutamate, and β-alanine). If the cell is exposed to the nonisotonic ECF for an extended period of time, the cell alters the intracellular levels of the organic osmolytes through metabolic processes.
•Fig. 2.6 The Gibbs-Donnan Effect. Top, TwosolutionsareseparatedbyamembranethatispermeablebyNa+ ,Cl− ,andH2Obutnotpermeablebyprotein(P−).TheosmolalityofsolutionAisidenticaltothatofsolutionB.Bottom, Cl− diffusesfromcompartmentBtocompartmentAdownitsconcentrationgradient.ThiscausescompartmentAtobecomeelectricallynegativewithregardtocompartmentB.ThemembranevoltagethendrivesthediffusionofNa+ fromcompartmentBtocompartmentA.TheaccumulationofadditionalNa+ andCl− incompartmentAincreasesitsosmolalityandcauseswatertoflowfromcompartmentBtocompartmentA(Note:theincreasevolumeofcompartmentAresultsinalower[P−]).IfthecontainercontainingthetwosolutionsweresealedatthetopsothatwatercouldnotmovefromcompartmentBtocompartmentA,thepressureincompartmentAwouldincreaseasthenumberofosmoticallyactiveparticlesincreasesinthatcompartment.
reduced from what would be caused by the Gibbs-Donnan effect, and cell volume is maintained in isotonic solutions.
Most cells throughout the body are bathed with isotonic ECF, the composition of which is tightly regulated (see ). However, certain regions within the body are not isotonic (e.g., the medulla of the kidney), and with disorders of water balance, the ECF can become either hypotonic or hypertonic. When this occurs, cells either swell or shrink. Cell swelling or shrinkage can result in cell damage or death, but many cells have mechanisms that limit the degree to which the cell volume changes. These mechanisms are particularly important for neurons, in which swelling within the confined space of the skull can lead to serious neurological damage.
In general, when a cell is exposed to nonisotonic ECF, volume-regulatory responses are activated within seconds to minutes to restore cell volume (
Fig. 2.7 ). With cell swelling, a regulatory volume decrease response transports osmotically active particles (osmolytes) out of the cell, reducing
TheECFofindividualswithdisordersinwaterbalancemaybeeitherhypotonic(positivewaterbalance)orhypertonic(negativewaterbalance).WithadecreaseinECFosmolality,neuronsandglialcellsswellaswaterentersthecell.Tominimizethisswelling,theneuronsandglialcellsreduceintracellularosmolytes.IftheECFosmolalityiscorrected(i.e.,increased)tooquickly,theneuronsandglialcellsthenshrinkbecauseofthereducednumberofintracellularosmolytes.ThisresponsetoarapidcorrectionofECFosmolalitycanleadtocelldamage.Damagetotheglialcellsthatsynthesizemyelinwithinthebraincanresultindemyelinization.Thisdemyelinizationresponse,termedosmotic demyelinization syndrome, canaffectanyofthewhitematterofthebrain,butespeciallyregionsofthepons.Theseeffectsareoftenirreversible.Therefore,correctionofdisordersofwaterbalanceisusuallyaccomplishedslowlytoavoidthisseriousneurologicalcomplication.